The long term goal of this research is to characterize the primary antibody repertoire and understand how it is generated. Our approach is to fully define the content and genetic organization of the mouse Igh-V locus by identifying V gene families and subfamilies and their relative map positions. The expression of V genes and V gene sets during development, in mature B cell population of different mouse strains and in B cell subsets will be examined using a powerful sampling assay recently developed in our laboratory. Studies are outlined to directly test: a) whether the expressed antibody repertoire differs among B cell subsets. Our studies of VH gene use in pre-B cells of a mutant mouse strain (xid) have led us to propose that B cell subsets us distinct VH gene rearrangement strategies. Will examine the VH repertoire of Lyl B cells by using two mutant mouse strains, xid (Lyl B-) and mevi (Lyl B+). We will do parallel experiments on VK gene expression both to confirm and extend our preliminary results suggesting preferential VK gene utilization in a VK rearranging cell line and to provide the first comprehensive analysis of VK gene family expression in the adult repertoire.